scholarly journals Allogenous Selection of Mutational Collateral Resistance: Old Drugs Select for New Resistance Within Antibiotic Families

2021 ◽  
Vol 12 ◽  
Author(s):  
Fernando Baquero ◽  
José L. Martínez ◽  
Ângela Novais ◽  
Jerónimo Rodríguez-Beltrán ◽  
Laura Martínez-García ◽  
...  

Allogeneous selection occurs when an antibiotic selects for resistance to more advanced members of the same family. The mechanisms of allogenous selection are (a) collateral expansion, when the antibiotic expands the gene and gene-containing bacterial populations favoring the emergence of other mutations, inactivating the more advanced antibiotics; (b) collateral selection, when the old antibiotic selects its own resistance but also resistance to more modern drugs; (c) collateral hyper-resistance, when resistance to the old antibiotic selects in higher degree for populations resistant to other antibiotics of the family than to itself; and (d) collateral evolution, when the simultaneous or sequential use of antibiotics of the same family selects for new mutational combinations with novel phenotypes in this family, generally with higher activity (higher inactivation of the antibiotic substrates) or broader spectrum (more antibiotics of the family are inactivated). Note that in some cases, collateral selection derives from collateral evolution. In this article, examples of allogenous selection are provided for the major families of antibiotics. Improvements in minimal inhibitory concentrations with the newest drugs do not necessarily exclude “old” antibiotics of the same family of retaining some selective power for resistance to the newest agents. If this were true, the use of older members of the same drug family would facilitate the emergence of mutational resistance to the younger drugs of the family, which is frequently based on previously established resistance traits. The extensive use of old drugs (particularly in low-income countries and in farming) might be significant for the emergence and selection of resistance to the novel members of the family, becoming a growing source of variation and selection of resistance to the whole family. In terms of future research, it could be advisable to focus antimicrobial drug discovery more on the identification of new targets and new (unique) classes of antimicrobial agents, than on the perpetual chemical exploitation of classic existing ones.

2021 ◽  
Author(s):  
Fernando Baquero ◽  
Jose-Luis martínez ◽  
Angela Silva-Novais ◽  
Jerónimo Rodríguez-Beltrán ◽  
Laura Martínez-García ◽  
...  

Allogeneous selection occurs when an antibiotic selects for resistance to more advanced members of the same family. The mechanisms of allogenous selection are (a) collateral expansion, when the antibiotic expands the gene and gene-containing bacterial populations favoring the emergence of other mutations, inactivating the more advanced antibiotics; (b) collateral selection, when the old antibiotic selects its own resistance but also resistances to more modern drugs; (c) collateral hyper-resistance, when resistance to the old antibiotic selects in higher degree for populations resistant to other antibiotics of the family than to itself; and (d) collateral evolution, when the simultaneous or sequential use of antibiotics of the same family selects for new mutational combinations with novel phenotypes, generally with higher activity or broader spectrum. Note that in some cases, collateral selection derives from collateral evolution. In this study, examples of allogenous selection are provided for the major families of antibiotics. Improvements in minimal inhibitory concentrations with the newest drugs do not necessarily exclude “old” antibiotics of the same family of retaining some selective power for resistance to the newest agents. If this were true, the use of older members of the same drug family would facilitate the emergence of mutational resistance to the younger drugs of the family, which is frequently based on previously established resistance traits. The extensive use of old drugs (particularly in low-income countries and in farming) might be significant for the emergence and selection of resistances to the novel members of the family, becoming a growing source of variation and selection of resistance to the whole family. In terms of future research, it could be advisable to focus antimicrobial drug discovery more on the identification of new targets and new (unique) classes of antimicrobial agents, than on the perpetual chemical exploitation of classic existing ones.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 491
Author(s):  
Sona Jain ◽  
Wanessa Santana ◽  
Silvio S. Dolabella ◽  
André L. S. Santos ◽  
Eliana B. Souto ◽  
...  

Leishmaniasis is one of the deadliest neglected tropical diseases affecting 12–15 million people worldwide, especially in middle- and low-income countries. Rapid and accurate diagnosis of the disease is important for its adequate management and treatment. Several techniques are available for the diagnosis of leishmaniasis. Among these, parasitological and immunological tests are most widely used. However, in most cases, the utilized diagnostic techniques are not good enough, showing cross-reactivity and reduced accuracy. In recent years, many new methods have been reported with potential for improved diagnosis. This review focuses on the diagnosis of Leishmania exploring the biosensors and nanotechnology-based options for their detection. New developments including the use of nanomaterials as fluorophores, fluorescence quenchers as reducing agents and as dendrimers for signal improvement and amplification, together with the use of aptamers to replace antibodies are described. Future research opportunities to overcome the current limitations on the available diagnostic approaches are also discussed.


Author(s):  
Giorgia Gon ◽  
Abdunoor M. Kabanywanyi ◽  
Petri Blinkhoff ◽  
Simon Cousens ◽  
Stephanie J. Dancer ◽  
...  

Abstract Background Healthcare associated infections (HAI) are estimated to affect up to 15% of hospital inpatients in low-income countries (LICs). A critical but often neglected aspect of HAI prevention is basic environmental hygiene, particularly surface cleaning and linen management. TEACH CLEAN is an educational intervention aimed at improving environmental hygiene. We evaluated the effectiveness of this intervention in a pilot study in three high-volume maternity and newborn units in Dar es Salaam, Tanzania. Methods This study design prospectively evaluated the intervention as a whole, and offered a before-and-after comparison of the impact of the main training. We measured changes in microbiological cleanliness [Aerobic Colony Counts (ACC) and presence of Staphylococcus aureus] using dipslides, and physical cleaning action using gel dots. These were analysed with descriptive statistics and logistic regression models. We used qualitative (focus group discussions, in-depth interviews, and semi-structured observation) and quantitative (observation checklist) tools to measure why and how the intervention worked. We describe these findings across the themes of adaptation, fidelity, dose, reach and context. Results Microbiological cleanliness improved during the study period (ACC pre-training: 19%; post-training: 41%). The odds of cleanliness increased on average by 1.33 weekly during the pre-training period (CI = 1.11–1.60), and by 1.08 (CI = 1.03–1.13) during the post-training period. Cleaning action improved only in the pre-training period. Detection of S. aureus on hospital surfaces did not change substantially. The intervention was well received and considered feasible in this context. The major pitfalls in the implementation were the limited number of training sessions at the hospital level and the lack of supportive supervision. A systems barrier to implementation was lack of regular cleaning supplies. Conclusions The evaluation suggests that improvements in microbiological cleanliness are possible using this intervention and can be sustained. Improved microbiological cleanliness is a key step on the pathway to infection prevention in hospitals. Future research should assess whether this bundle is cost-effective in reducing bacterial and viral transmission and infection using a rigorous study design.


Author(s):  
Alexandra E. Hill ◽  
Izaac Ornelas ◽  
J. Edward Taylor

The labor supply response to agricultural wages is critical to the viability of crop production in high-income countries, which hire a largely foreign farm work force, as well as in low-income countries, where domestic workers move off the farm as the agricultural transformation unfolds. Modeling agricultural labor supply is more challenging than modeling the supply of other agricultural inputs or of labor to other sectors of the economy owing to unique features of agricultural production and farm labor markets. Data and econometric challenges abound, and estimates of agricultural labor supply elasticities are sparse. This review explains the importance and challenges of modeling farm labor supply and describes researchers’ efforts to address these challenges. It summarizes estimates of agricultural labor supply elasticities over the last 80 years, provides insights into variation in these estimates, identifies priority areas for future research, and reviews the most influential empirical work related to this important topic. Expected final online publication date for the Annual Review of Resource Economics, Volume 13 is October 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.


Water ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 429 ◽  
Author(s):  
Charles Nanseu-Njiki ◽  
Willis Gwenzi ◽  
Martin Pengou ◽  
Mohammad Rahman ◽  
Chicgoua Noubactep

Inadequate access to safe drinking water is one of the most pervasive problems currently afflicting the developing world. Scientists and engineers are called to present affordable but efficient solutions, particularly applicable to small communities. Filtration systems based on metallic iron (Fe0) are discussed in the literature as one such viable solution, whether as a stand-alone system or as a complement to slow sand filters (SSFs). Fe0 filters can also be improved by incorporating biochar to form Fe0-biochar filtration systems with potentially higher contaminant removal efficiencies than those based on Fe0 or biochar alone. These three low-cost and chemical-free systems (Fe0, biochar, SSFs) have the potential to provide universal access to safe drinking water. However, a well-structured systematic research is needed to design robust and efficient water treatment systems based on these affordable filter materials. This communication highlights the technology being developed to use Fe0-based systems for decentralized safe drinking water provision. Future research directions for the design of the next generation Fe0-based systems are highlighted. It is shown that Fe0 enhances the efficiency of SSFs, while biochar has the potential to alleviate the loss of porosity and uncertainties arising from the non-linear kinetics of iron corrosion. Fe0-based systems are an affordable and applicable technology for small communities in low-income countries, which could contribute to attaining self-reliance in clean water supply and universal public health.


2019 ◽  
Vol 11 (22) ◽  
pp. 6249 ◽  
Author(s):  
Shahram Heydari ◽  
Adrian Hickford ◽  
Rich McIlroy ◽  
Jeff Turner ◽  
Abdulgafoor M. Bachani

Road safety in low-income countries (LICs) remains a major concern. Given the expected increase in traffic exposure due to the relatively rapid motorisation of transport in LICs, it is imperative to better understand the underlying mechanisms of road safety. This in turn will allow for planning cost-effective road safety improvement programs in a timely manner. With the general aim of improving road safety in LICs, this paper discusses the state of knowledge and proposes a number of future research directions developed from literature reviews and expert elicitation. Our study takes a holistic approach based on the Safe Systems framework and the framework for the UN Decade of Action for Road Safety. We focused mostly on examining the problem from traffic engineering and safety policy standpoints, but also touched upon other sectors, including public health and social sciences. We identified ten focus areas relating to (i) under-reporting; (ii) global best practices; (iii) vulnerable groups; (iv) disabilities; (v) road crash costing; (vi) vehicle safety; (vii) proactive approaches; (viii) data challenges; (ix) social/behavioural aspects; and (x) capacity building. Based on our findings, future research ought to focus on improvement of data systems, understanding the impact of and addressing non-fatal injuries, improving estimates on the economic burden, implementation research to scale up programs and transfer learnings, as well as capacity development. Our recommendations, which relate to both empirical and methodological frontiers, would lead to noteworthy improvements in the way road safety data collection and research is conducted in the context of LICs.


2019 ◽  
Vol 8 (1) ◽  
Author(s):  
Sehlisiwe R. Ndlovu ◽  
Desmond Kuupiel ◽  
Themba G. Ginindza

Abstract Background Paediatric cancers account for a minor fraction of deaths and hence receive little attention from policymakers. In low-income countries, the absence of comprehensive national paediatric strategies results in a lack of access for a majority of children with cancer. In sub-Saharan Africa (SSA), the burden of childhood cancers is underestimated due to a lack of paediatric cancer registries, poor health care systems and competing healthcare needs. The objective of this study is to map evidence on the distribution of paediatric cancers in the SSA region. Method A scoping review will be conducted to map literature on the distribution of paediatric cancers in SSA. An electronic literature search will be conducted from the following databases: PubMed, Google Scholar, EBSCOhost (CINAHL and Health Source) and World Health Organization (WHO)/International Agency for Research in Cancer (IARC) (GLOBOCAN databases). We will also search the reference lists of included studies to source relevant literature. A pilot search was conducted to determine the feasibility of the study. Study selection will be guided by the inclusion and exclusion criteria. After charting the data, a descriptive overview of the studies will be presented in a narrative format. An account of the study characteristics will be described in this narrative. The analysis will be mainly based on mapping the country-specific outcomes emerging from the studies, and a numerical summary of these outcomes will be conducted. Tables, maps and charts will be produced and presented in the result section. Discussion This review study will identify existing research gaps for future research to influence policy implementation and to improve the availability of diagnosis and treatment of paediatric cancers in SSA.


2000 ◽  
Vol 17 (2) ◽  
pp. 90-96 ◽  
Author(s):  
Robert A. Hayes ◽  
Lisa A. Efron ◽  
Gina S. Richman ◽  
Kelley A. Harrison ◽  
Elizabeth L. Aguilera

AbstractThe current study demonstrates the efficacy of using a behavioural contingency contract in conjunction with family-selected reinforcers to increase appointment keeping among low income families in a child and family therapy clinic. Three families with similar presenting problems participated. A multiple baseline across-subjects design with the addition of a reversal component was utilised. Upon treatment implementation, contracts were signed by family members stating that they would receive coupons valuing $30.00 after attending four consecutive clinic appointments. These coupons were selected by the family from a diverse menu. Results indicated increases in appointment keeping following implementation of the behavioural contract. The cost effectiveness of using a behavioural contract in conjunction with economic incentives with low-income families is discussed, and suggestions for future research on appointment keeping are made.


2012 ◽  
Vol 03 (02) ◽  
pp. 1250005 ◽  
Author(s):  
ARUN S. MALIK ◽  
STEPHEN C. SMITH

We put in perspective the papers in this special issue by characterizing different forms of adaptation to climate change and discussing the role of adaptation in a developing country context. We highlight adaptation decision-making under uncertainty, empirics of autonomous adaptation, and data and methodological challenges. We identify unresolved questions, emphasizing interactions between autonomous and planned adaptation, adaptation externalities, and the relationship between adaptation and conflict.


1998 ◽  
Vol 42 (11) ◽  
pp. 2914-2918 ◽  
Author(s):  
Glenn A. Pankuch ◽  
Shane A. Jueneman ◽  
Todd A. Davies ◽  
Michael R. Jacobs ◽  
Peter C. Appelbaum

ABSTRACT Selection of resistance to amoxicillin (with or without clavulanate), cefaclor, cefuroxime, and azithromycin among six penicillin G- and azithromycin-susceptible pneumococcal strains and among four strains with intermediate penicillin sensitivities (azithromycin MICs, 0.125 to 4 μg/ml) was studied by performing 50 sequential subcultures in medium with sub-MICs of these antimicrobial agents. For only one of the six penicillin-susceptible strains did subculturing in medium with amoxicillin (with or without clavulanate) lead to an increased MIC, with the MIC rising from 0.008 to 0.125 μg/ml. Five of the six penicillin-susceptible strains showed increased azithromycin MICs (0.5 to >256.0 μg/ml) after 17 to 45 subcultures. Subculturing in medium with cefaclor did not affect the cefaclor MICs of three strains but and led to increased cefaclor MICs (from 0.5 to 2.0 to 4.0 μg/ml) for three of the six strains, with MICs of other β-lactams rising 1 to 3 twofold dilutions. Subculturing in cefuroxime led to increased cefuroxime MICs (from 0.03 to 0.06 μg/ml to 0.125 to 0.5 μg/ml) for all six strains without significantly altering the MICs of other β-lactams, except for one strain, which developed an increased cefaclor MIC. Subculturing in azithromycin did not affect β-lactam MICs. Subculturing of the four strains with decreased penicillin susceptibility in amoxicillin (with or without clavulanate) or cefuroxime did not select for β-lactam resistance. Subculturing of one strain in cefaclor led to an increase in MIC from 0.5 to 2.0 μg/ml after 19 passages. In contrast to strains that were initially azithromycin susceptible, which required >10 subcultures for resistance selection, three of four strains with azithromycin MICs of 0.125 to 4.0 μg/ml showed increased MICs after 7 to 13 passages, with the MICs increasing to 16 to 32 μg/ml. All azithromycin-resistant strains were clarithromycin resistant. With the exception of strains that contained mefE at the onset, no strains that developed resistance to azithromycin containedermB or mefE, genes that have been found in macrolide-resistant pneumococci obtained from clinic patients.


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